Investigations into the possible immunologic basis of human uveitidies has necessitated the development of animal models. Several forms of experimental allergic uveitis (EAU) have been produced by various immunizing preparations. Cellular and humoral immune responses to the inciting preparation have been demonstrated in animals exhibiting EAU. In our laboratory we have been studying EAU in guinea pigs injected with an extract of homologous retina homogenate (S preparation). Recent work has revealed a crossreaction of anti-S serum with pineal gland. Furthermore we have preliminary evidence of cellular infiltrate and loss of antigen reactivity in pineal gland of animals exhibiting EAU. It is proposed that we further study the role of the pineal in S induced EAU in the guinea pig and rabbit both in the homologous and heterologous system. A more complete picture of the relationship of pineal and retina will be gained by studying pineal induced EAU or at least the immune response of animals to pineal homogenate. Because the ocular immune response is not necessarily reflected in the systemic response, a comparison of local and systemic, cellular and humoral responses will be made. A clearer understanding of the immune mechanisms and species specificity involved in S induced EAU should then allow us to examine human uveitic patients for similar immune responses. Identification of common parameters will allow us to concentrate our efforts in those areas where the animal model is similar to the human disease state. If S induced EAU is a model for human autoimmune disease, pineal involvement could be significant when one considers those forms of uveitis that have extraocular manifestations. An understanding of the scope of the immune mechanisms involved in these diseases should allow for improved management of the patient.